The purpose of the study described in this application is to examine the potential correlation between the difference in the TMEV-specific TCR repertoire and the development of TMEV-induced demyelination. Four specific aims are proposed:1) To determine Vb and Jb usage by TMEV-specific and non specific CNS-infiltrating T cells during active demyelination. 2) To compare the T cells in CNS after intracerebral infection with pathogenic and low-pathogenic TMEV.3) To assess changes in the TCR repertoire of infiltrating T cells after alteration of the disease course by immunization with TMEV epitopes. 4) To analyze potential effects of susceptible H-2Ds and resistant J-2Dd loci on the selection of the TCR repertoire specific for TMEV antigens. Both immunological and molecular biological approaches will be employed towards achievement of the objectives of this project.